Compositions and methods for treating neurodevelopmental disorders
Methods of treating neurodevelopmental disorders by administering an acetylated amino acid having a carbon-nitrogen bond and acetyl group covalently bound to the nitrogen of the carbon-nitrogen bond and having a three-dimensional structure that allows the acetylated amino acid to enter cells and neurons are described. In one embodiment, the acetylated amino acid is a compound of Formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , and R 14 is each independently H or D, or a pharmaceutically acceptable salt thereof. Pharmaceutical compositions containing the acetylated amino acid are also described.
1. A method for treating a neurodevelopmental disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I):
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , and R 14 is each independently H or D; or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the neurodevelopmental disorder is selected from a group consisting of SYNGAP1-Related Disorder, SLC6A1-Related disorder, MED13L syndrome, CTNNB1 syndrome, DLG4-related synaptopathy, KCNT1 epilepsy, FOXG1 syndrome, Autism Spectrum Disorder, Attention-Deficit Disorder and Intellectual Disability.
3. The method of claim 1 , wherein the neurodevelopmental disorder is a developmental and epileptic encephalopathy.
4. The method of claim 3 , wherein the developmental and epileptic encephalopathy is SYNGAP1-Related Disorder.
5. The method of claim 1 , wherein the compound of Formula (I) is N-acetyl-L-leucine.
6. The method of claim 5 , wherein N-acetyl-L-leucine is administered orally.
7. The method of claim 6 , wherein from about 100 mg to about 5 grams of N-acetyl-L-leucine is administered per day.
8. The method of claim 6 , wherein N-acetyl-L-leucine is administered in a pharmaceutical composition comprising N-acetyl-L-leucine and one or more pharmaceutically acceptable excipients.
9. The method of claim 8 , wherein the pharmaceutical composition further comprises N-acetyl-D-leucine.
10. The method of claim 8 , wherein the pharmaceutical composition consists of N-acetyl-L-leucine and one or more pharmaceutically acceptable excipients.
11. The method of claim 8 , wherein the pharmaceutical composition is a solution comprising N-acetyl-L-leucine dissolved in a pharmaceutically acceptable solvent.
12. The method of claim 6 , wherein N-acetyl-L-leucine is administered twice or three times a day.
13. The method of claim 1 , wherein the subject is a carrier of a SYNGAP1 pathogenic gene mutation.
14. A method for treating a neurodevelopmental disorder comprising administering to a subject in need thereof a therapeutically effective amount of N-acetyl-DL-leucine.
15. The method of claim 14 , wherein the neurodevelopmental disorder is selected from a group consisting of SYNGAP1-Related Disorder, SLC6A1-Related disorder, MED13L syndrome, CTNNB1 syndrome, DLG4-related synaptopathy, KCNT1 epilepsy, FOXG1 syndrome, Autism Spectrum Disorder, Attention-Deficit Disorder and Intellectual Disability.
16. The method of claim 14 , wherein the neurodevelopmental disorder is a developmental and epileptic encephalopathy.
17. The method of claim 14 , wherein N-acetyl-DL-leucine is administered orally.
18. The method of claim 17 , wherein N-acetyl-DL-leucine is administered twice or three times a day.
19. The method of claim 14 , wherein N-acetyl-DL-leucine is administered in a pharmaceutical composition comprising N-acetyl-DL-leucine and one or more pharmaceutically acceptable excipient(s), and the pharmaceutical composition is a liquid comprising N-acetyl-DL-leucine dissolved in a solvent.
20. The method of claim 17 , wherein from about 200 mg to about 10 grams of N-acetyl-DL-leucine is administered per day.